2-(4-Isobutylphenyl)-propionic acid (ibuprofen) is an analgesic, antipyretic, anti-inflammatory drug that has the following chemical formula:

Ibuprofen is a drug that has become very well known since its invention in the 1960s, and is currently marketed for the treatment of pain, inflammation and fever, under a variety of trade names in pharmaceutical forms for oral administration.
Ibuprofen can be in the form of the (R) or (S) enantiomers, and although it is the (S) enantiomer that is biologically active, the majority of preparations contain the racemic mixture, since the (R) enantiomer is converted to the active form (S) in vivo. Hereinafter, “ibuprofen” is to mean either of the two enantiomers, (R) or (S), or the racemate.
Despite its many advantages, one of the main drawbacks of ibuprofen is, however, its poor solubility in water. Ibuprofen is a monoprotic acid with pKa=4.4. Its solubility is therefore closely related to pH, and may vary from 78 micrograms/mL at acidic pHs to 291 mg/mL at alkaline pHs. As a result, the development of certain dosage forms of ibuprofen, in particular liquid dosage forms for injection, has been problematic.
Thus, for example, international publications WO 03/039532 A1 and WO 2005/065674 A1 describe liquid pharmaceutical compositions of ibuprofen that include amino acids such as arginine for improving the solubility of ibuprofen, and that have pH values below 7.8. However, these formulations have the drawback that, although they can be submitted to thermal treatment up to a certain degree, they cannot be autoclaved since in the conditions of autoclave sterilization, i.e. generally for 15 minutes at 121° C., the arginine would decompose, generating unforeseeable impurities. This means that such formulations cannot be submitted to the aforesaid autoclaving procedure, which is the method of sterilization that must be used as first choice and is the most advisable for any injectable pharmaceutical formulation.
An injectable pharmaceutical composition of ibuprofen is already marketed with the trade name Caldolor, with composition according to the formulation described in the international publications cited above, and which is indicated for the treatment of moderate to severe pain and for fever. This formulation contains, per 1 mL of solution, 100 mg of ibuprofen in water for injection (therefore at a concentration of 100 mg/mL of ibuprofen) and 78 mg of arginine, at arginine:ibuprofen molar ratio of 0.92:1, in glass vials that contain 400 or 800 mg of ibuprofen, and at a pH of about 7.4. This formulation, however, is very concentrated for direct use and requires subsequent dilution to 100 or 200 millilitres. Moreover, as already mentioned, it cannot be autoclaved, thus necessitating very expensive aseptic manufacture.
Pharmaceutical formulations for parenteral use that contain ibuprofen at a concentration of 8 mg/mL and trometamol (tris-hydroxymethyl-aminomethane) at a concentration of 6.04 mg/mL, the pH being limited to the range 7.8-8.2, are also known from DE 199 12 436 A1 and its subsequent international publication WO 00/56325. However, this document neither describes nor suggests formulations with other values of concentration of the stated components, or with pH values outside of the stated range. In addition, the relatively high content of ibuprofen in the compositions disclosed in this document may compromise the solubility of ibuprofen at the pH of the composition, and the additional fact that the sterilization of these compositions was carried out by sterile filtration suggests that these compositions were possibly not suitable for sterilization in autoclave. This unsuitability has anyway been demonstrated through comparative experimental tests reported hereinbelow.